P3.2 Clinical evaluation (Section 2)
Page last updated: September 2016
Additional Information Requests
- For a proposed combination vaccine, assess whether there is any clinically important loss of beneficial effectiveness when antigens are combined, compared with when they are given individually (Section 2)
To assess comparative harms:
- explain how adverse events were ascertained in the trials (Subsection 2.5)
- provide any information on adverse reactions that might have arisen following launch of the proposed vaccine in other markets (Subsection 2.7)
Where the assessment of a vaccine is based on short-term surrogates, discuss long-term outcomes, such as waning of effect and resulting disease, and long-term sequelae.
Discuss any implications of co-administration with other vaccines.
P3.2.1 Noninferiority assessment (Section 2)
As discussed in Subsection P1.1, the components of a vaccine combination product should have an additive (not necessarily synergistic) beneficial effectiveness. For a vaccine that combines antigens, there should be no loss of beneficial effectiveness of each of the components. For example, if there is any reduction in titres for any components of a fixed combination vaccine product compared with its individual component products, the noninferiority assessment would be whether this would be expected to reduce the overall vaccine effectiveness to a clinically important extent. Subsection 2.4.5 contains guidance for comparing the proposed combination vaccine product with each of its individual components (ie assessing noninferiority). Further guidance on assessing fixed-dose combination products is given in Sections P1.1.1–P1.1.5.
P3.2.2 Superiority claims based on immunogenicity surrogates/correlates
Unless there are internationally accepted standards of measurement, the criteria developed to support any claims of superiority based on immunogenicity surrogates/correlates rather than clinically important outcomes must be prespecified and justified, and their limitations addressed. (See also Subsection 3A.5.)
P3.2.3 Comparative harms and adverse reactions (Subsections 2.5–2.7)
Ensure that the assessment of comparative harms extends beyond those temporally associated with the administration of the vaccine to those that might emerge some time after the vaccine course is completed. This might include the consequences of possibly delaying, rather than preventing, disease because of changes in disease epidemiology and individual susceptibility at a population level at a certain time.
Present evidence of the effectiveness of the vaccine for individuals in the primary and catch-up populations.